Biology Reference
In-Depth Information
duplicated gene sequences (Eichler
et al
., 1998a). The chromosome 16
SLC6A8
paralogue (
SLC6A10
) retained both its putative promoter and transcriptional
activity (Iyer
et al
., 1996) but the chromosome 16 CDM paralogue clearly repre-
sents a truncated pseudogene. A very similar Xq28-16p11 transposition, reported
by Eichler
et al
. (1997), involves the independent transposition of a 9.7 kb seg-
ment encompassing exons 7-10 of the adrenoleukodystrophy (
ALD
; Xq28) gene
to the pericentromeric regions of chromosomes 2p11, 10p11, 16p11, and 22q11).
This
ALD
paralogy domain lies only 27 kb telomeric to the
SLC6A8/
CDM paral-
ogy domain (
Figure 9.4
). The autosomal sequences represent truncated non-
processed pseudogenes with sequence divergence being consistent with the
duplication/transposition events having occurred between 5 Myrs and 10 Myrs
ago. As far as the
ALD
transposition events are concerned, an initial event
directed to chromosome 2p11 appears to have served as a 'seed' for further peri-
centromeric-directed transposition events to occur (
Figure 9.4
). An inverted clus-
ter of
Alu
repeats lies in the vicinity of the Xq28 breakpoint. In addition, Eichler
et al
. (1997) noted the presence of a GCTTTTTGC repeat flanking the duplicated
region which they speculated might serve as a sequence-specific integration site
for transposition. Such a sequence may provide a hyper-recombinogenic signal
which could account for the propensity of this locus to be involved in transposi-
tional events.
Other pericentromeric-directed duplications/transpositions in the human
genome (reviewed by Eichler 1998) involve the immunoglobulin V
light chain
Xq28
SLC6A8/CDM
Paralogy Domain
ALD
Paralogy Domain
SLC6A8
CDM ALD
CEN
TEL
Kb
10
20
30
40
50
60
2p11
16p11
10p11
22q11
Figure 9.4.
Pericentromeric-directed transposition events from the
ALD
/
SLC6A8
locus
at Xq28 to other chromosomes. An initial duplication/transposition targeted
chromosome 2p11 from where subsequent transposition events were directed to 16p11,
10p11, and 22q11. The paralogy domains encompassing, (i) the
SLC6A8
and
CDM
genes,
and (ii) the
ALD
gene are boxed. CEN, centromere; TEL, telomere.
